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PurposeThis study examined relations between four late-life depression subgroups (recent, >2 years ago, chronic, no depression) and regional brain volumes using structural MRI data from the National Alzheimer’s Coordinating Center (n=1,551). Data AnalysisMultiple linear regressions evaluated the effects of depression on 30 MRI biomarkers, while moderation analyses assessed how APOE ε4 and depression shape the connections between cognitive status and brain structure volumes. ResultsAfter adjusting for covariates and applying Hochberg’s method, recent depression (< 2 years) was associated with reduced total cerebrum cranial volume and left frontal lobe cortical gray matter volume. Chronic depression correlated with larger right lateral ventricle volume. ConclusionThese findings suggest that recent depression is linked to brain atrophy across specific regions and ventricular enlargement. Future research should investigate age-related impacts on these associations and whether restoration of brain volume occurs after depressive symptoms subside.